Elsevier

Injury

Volume 40, Issue 8, August 2009, Pages 851-855
Injury

Modulation of the innate immune response after trauma visualised by a change in functional PMN phenotype

https://doi.org/10.1016/j.injury.2008.11.002Get rights and content

Abstract

Background

Acute Respiratory Distress Syndrome (ARDS) is a frequent and severe complication after trauma, caused by an excessive inflammatory response mediated by polymorphonuclear granulocytes (PMNs). It was previously demonstrated that patients with activated PMNs in the lungs have PMNs in the peripheral circulation with a reduced active FcγRII up-regulating capacity. We tested the hypothesis that a correlation exists between the severity of inflammation and the extent of decreased responsiveness of active FcγRII on circulating PMNs, as a sign of altered immunological capacity.

Methods

Fifty-two patients were included and injury severity was assessed by clinical injury severity scores and base deficit. Symptoms and signs of inflammation were recorded on a daily basis and fMLP-induced active FcγRII on PMNs was assessed by FACS analysis within 24 h after injury. Results were compared with 10, age matched healthy controls.

Results

The baseline PMN membrane expression of Mac-1/CD11b and active FcγRII/CD32 did not correlate with injury severity. Levels of the acute phase protein Interleukin 6 (IL-6) correlated significantly with injury severity, indicating that a range in severity of the inflammatory response was present in the studied population. A statistically significant correlation between the PMN responsiveness towards the bacterial derived peptide fMLP of active FcγRII and injury severity was demonstrated. In addition, decreasing responsiveness of active FcγRII on PMNs was found in patients who developed systemic inflammatory response syndrome (SIRS) or acute lung injury (ALI)/ARDS.

Conclusions

The extent of the sustained injury and the subsequent cellular innate immune response is reflected by changes in a functional PMN phenotype of fMLP-induced active FcγRII in the peripheral blood.

Introduction

The Acute Respiratory Distress Syndrome (ARDS) is a frequent and severe complication after trauma. Although the mortality and morbidity rates of ARDS have decreased over the last decade, the incidence remains high.2, 28 Polymorphonuclear granulocytes (PMNs) play an essential role in the development of ARDS. In experimental animal models of ARDS, high numbers of PMNs are found in the pulmonary interstitium.4, 29 PMN depletion or blocking of PMN extravasation protects animals for the development of ARDS in severe trauma models.6, 10, 18 This prominent role of PMNs is emphasised by the correlation between the extent of ischaemia reperfusion injury and the accumulation of PMNs in the pulmonary interstitium.25, 26

In patients, PMN activation is mostly measured by static phenotype characteristics or reactive oxygen species (ROS) production, however, with contradictory results. We have recently demonstrated that after trauma PMNs in the peripheral circulation have a decreased responsiveness of active FcγRII, an opsonin receptor related to antibody recognition. This represents the altered functionality of these cells. In the same patients the PMNs in the pulmonary interstitium demonstrated an activated phenotype and function.11 We hypothesised that this altered functional PMN phenotype, measured by PMN receptor analysis in whole blood, could be used as a read out of the inflammatory response to injury. In addition, it was investigated whether these putative changes in PMN responsiveness were associated with the development of signs and symptoms of severe systemic inflammation (systemic inflammatory response syndrome [SIRS] and ARDS).

Section snippets

Patients

Patients with a wide range of injury severity were chosen in order to investigate the relationship between trauma severity and PMN receptor expression. Fifty-two trauma patients with an ISS (Injury Severity Score) >3 and admitted to the Department of Traumatology, University Medical Centre Utrecht were included. Exclusion criteria were age <16 or >80 years, death within 6 h after admission and patients with an altered immunological status (e.g. corticosteroid use or chemotherapy). A blood sample

Patient demographics

Fifty-two consecutive trauma patients were included with varying severities of their injuries. Their mean age was 34 years (interquartile range 20–49) and the mean ISS was 10 (interquartile range 9–17). In total, 12 patients needed transfusion (packed red blood cells). However, in our cohort, only 1 patient required >10 packed red blood cells. Five patients suffered from severe head trauma, moreover, all 5 patients suffered from additional thorax injury. Nine patients fulfilled the SIRS

Discussion

We found a decreased responsiveness of active FcγRII towards the bacterial peptide fMLP on the circulating PMN population after trauma. The extent of this reduced responsiveness correlated with the burden of trauma, estimated by injury severity scores and base deficit levels (Table 6). More importantly, the extent of decrease in fMLP-induced active FcγRII on PMNs was related to severity of the clinical expression of the systemic inflammatory response, such as SIRS and ALI/ARDS.

In contrast, no

Acknowledgement

This project was funded by the AO Foundation, grant S-06-14H.

References (29)

  • P.V. Giannoudis et al.

    Stimulation of inflammatory markers after blunt trauma

    Br J Surg

    (1998)
  • P.J. Harwood et al.

    Which AIS based scoring system is the best predictor of outcome in orthopaedic blunt trauma patients?

    J Trauma

    (2006)
  • P.J. Harwood et al.

    Alterations in the systemic inflammatory response after early total care and damage control procedures for femoral shaft fracture in severely injured patients

    J Trauma

    (2005)
  • L.A. Hernandez et al.

    Role of neutrophils in ischemia-reperfusion-induced microvascular injury

    Am J Physiol

    (1987)
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